NERVE GROWTH-FACTOR TRIGGERS MICROFILAMENT ASSEMBLY AND PAXILLIN PHOSPHORYLATION IN HUMAN B-LYMPHOCYTES

Citation
I. Melamed et al., NERVE GROWTH-FACTOR TRIGGERS MICROFILAMENT ASSEMBLY AND PAXILLIN PHOSPHORYLATION IN HUMAN B-LYMPHOCYTES, The Journal of experimental medicine, 181(3), 1995, pp. 1071-1079
Citations number
38
Categorie Soggetti
Immunology,"Medicine, Research & Experimental
ISSN journal
00221007
Volume
181
Issue
3
Year of publication
1995
Pages
1071 - 1079
Database
ISI
SICI code
0022-1007(1995)181:3<1071:NGTMAA>2.0.ZU;2-X
Abstract
Increasing evidence suggests that the nervous system is involved in al lergic inflammation. One of the potential regulatory molecules of the neuroimmune system is nerve growth factor (NGF). Recent studies from o ur group demonstrated the presence of a functional NGF receptor (NGFR) on human B lymphocytes. Moreover, we showed that gp140(trk) tyrosine kinase, which serves as an NGFR, was involved in transduction of early signaling events in human B lymphocytes. The mechanisms by which NGF initiates the signaling cascade and the link between the neuroimmune s ystems are unknown. We have focused on the role of the cytoskeleton as a possible mediator for transduction of signals induced by NGE Polyme rized actin (F-actin) content was determined by fluorescent staining a nd immunoblotting with antiactin antibody. Addition of NGF caused a ti me- and concentration-dependent increase in F-actin content, and maxim um effects were noted after 1 min. These increases in F-actin content and NGF-induced thymidine incorporation could be blocked by incubating the cells with cytochalasin D and botulinum C-2 toxin before the addi tion of NGF. Incubation of human B lymphocytes with 10 nM K252a, an in hibitor of Trk kinase, decreased NGF-induced microfilament assembly by 75%. In immunoprecipitation experiments, addition of NGF to B cells i nduced a rapid increase in the tyrosine phosphorylation of paxillin, o ne of a group of focal adhesion proteins involved in linking actin fil aments to the plasma membrane. Coimmunoprecipitation studies demonstra ted the association between gp140(trk) kinase and paxillin. Together, these observations suggest that actin assembly is involved in NGF sign aling in human B cells, and that paxillin may be essential in this pat hway after phosphorylation by gp140(trk) kinase.